Eukaryotic Release Factor (eRF) Degrader

PROTAC erf3a Degrader-1 (Compound C63) is an orally active PROTAC erf3a Degrader. PROTAC erf3a Degrader-1 inhibits cancer cell proliferation (eg: 22Rv1). PROTAC erf3a Degrader-1 can be used for research of prostate cancer, ovarian cancer, liver cancer, cervical cancer, leukemia, breast cancer.

XYD049 is a CRBN-based molecular glue degrader targeting GSPT1, with a DC₅₀ of 19 nM. XYD049 mediates the formation of a ternary complex between CRBN and GSPT1, thereby triggering CRBN- and proteasome-dependent degradation of GSPT1. By degrading GSPT1, XYD049 downregulates castration-resistant prostate cancer (CRPC)-related oncogenes, including BCL2, CDK2, E2F3, EGFR, HSP90B1, TMPRSS2, AR, AR-V7, PSA and c-Myc. XYD049 inhibits cancer cell growth and suppresses tumor growth in mice. XYD049 can be used for research on castration-resistant prostate cancer. XYD049 consists of a linker (black part) NH2-C5-NH-Boc (HY-W004710), a CRBN-based E3 ligase ligand (blue part) Thalidomide 4-fluoride (HY-41547), and a target protein ligand (red part) GSPT1 ligand-1 (HY-170821), among which the E3 ligase ligand plus linker forms the conjugate E3 Ligase Ligand-linker Conjugate 158 (HY-170822).

GSPT1 degrader-15 (Compound Lib-B-15O) is a potent and highly selective GSPT1 molecular gel degrader, with a DC₅₀ of 154 nM. GSPT1 degrader-15 has almost no effect on the expression of other proteins. GSPT1 degrader-15 exhibits significant anti-proliferative activity against leukemia cells and lymphoma cells. GSPT1 degrader-15 can be used in leukemia and lymphoma research.

XYD113 is an orally active, selective GSPT1 Molecular glue degrader. XYD113 promotes the formation of the CRBN-GSPT1 ternary complex and mediates GSPT1 degradation in a CRBN-dependent manner via the ubiquitin-proteasome system. XYD113 downregulates genes associated with the occurrence and progression of prostate cancer (c-Myc, AR, AR-V7, KLK3, KLK2, TMPRSS2). XYD113 exhibits anticancer activity against prostate cancer. XYD113 can be used in the research of prostate cancer.

FM-74-103 is a selective GSPT1 PROTAC degrader and broad-spectrum antiviral agent. FM-74-103 recruits GSPT1 to the Cereblon E3 ligase to form a ternary complex, thereby driving GSPT1 ubiquitination and proteasomal degradation. FM-74-103 inhibits the replication of IAV, SARS-CoV-2 and CMV (including Nucleozin (HY-50001)-resistant influenza A virus). FM-74-103 can be used in research related to influenza A virus infection, SARS-CoV-2 infection and cytomegalovirus infection.

GSPT1 degrader-13 is a selective molecular glue GSPT1 degrader. GSPT1 degrader-13 exhibits antiproliferative activity against cancer cells in a CRBN- and GSPT1-dependent manner. GSPT1 degrader-13 can be used for leukemia research.

GSPT1 degrader-4 is a GSPT1 molecular glue degrader that recruits cereblon (CRBN), with a DC₅₀ of 25.4 nM. GSPT1 degrader-4 inhibits the proliferation of cancer cells. GSPT1 degrader-4 is applicable to breast cancer-related research.

GSPT1 degrader-16 (Compound Lib-B-18J) is a potent and selective cereblon-based molecular glue degrader that targets G1 to S phase transition 1 (GSPT1). GSPT1 degrader-16 shows inhibitory effect to RS4;11, Molt4, and MM.1S cells with IC₅₀ values of 0.002, 0.26 and 0.37 μM. GSPT1 degrader-16 can be used for the research of cancer, such as acute lymphoblastic leukemi.

TD-522 is a potent and selective molecular glue GSPT1 degrader, with a DC₅₀ of 0.269 nM. TD-522 exhibits strong anti-proliferative effects and induces apoptosis in acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) cells. TD-522 suppresses tumor growth in a TMD-8 xenograft model. TD-522 can be used for AML and DLBCL research.

GSPT1 degrader-8 is a potent and orally active G1 to S phase transition 1 (GSPT1) molecular glue degrader. GSPT1 degrader-8 induces GSPT1 degradation and inhibits tumor growth. GSPT1 degrader-8 can be used for the research of cancer, such as breast cancer.

BWA-6047 is an oral active PROTAC degrader targeting AR/AR-V7 and GSPT1 with DC₅₀ values of 3.7, 3.0 and 1.2 nM in 22Rv1 cells. BWA-6047 suppresses the expression of AR downstream target genes and and transcriptional activity. BWA-6047 inhibits cancer cells proliferation, causes G1 phase cell cycle arrest and induces apoptosis. BWA-6047 increases cleaved-PARP-1 and cleaved-caspase-3 levels. BWA-6047 reduces growth of LNCaP xenograft tumors in mice models without obvious toxicity. BWA-6047 can be used for the research of prostate cancer.

AG6033 is a CRBN-dependent molecular glue degrader targeting GSPT1 (DC₅₀ of 2.5 μM) and IKZF1. AG6033 induces degradation of GSPT1 via π-π stacking and hydrogen bonding with CRBN in a partially CRBN-dependent manner, decreases IKZF1 levels, and promotes degradation of CRBN substrates. AG6033 induces apoptosis in lung adenocarcinoma cells. AG6033 can be used for the research of lung cancer.

GSPT1 degrader-1 is a highly selective degrader targeting GSPT1. GSPT1 degrader-1 induces degradation via the ubiquitin-proteasome system. GSPT1 degrader-1 induces G₀/G₁ phase arrest, apoptosis (apoptosis) and inhibits proliferation in leukemia cells. GSPT1 degrader-1 reduces the levels of CDK6 and Cyclin B1, while increases the levels of activated caspase-3 and caspase-9 in leukemia cells. GSPT1 degrader-1 can be used in leukemia research.

DIX-01 is a CRBN-recruiting molecular glue and cytotoxic agent targeting GSPT1, with an EC₅₀ of 173 nM against human GSPT1. DIX-01 drives proteasomal degradation of GSPT1, IKZF1 and IKZF3, and induces cytotoxicity in cancer cells. DIX-01 inhibits tumor growth in a zebrafish xenograft model and can be used for research on acute myeloid leukemia and prostate cancer.

GSPT1 degrader-2 is an orally active GSPT1 molecular glue degrader that promotes the degradation of intracellular GSPT1 protein, with DC₅₀ values of 3 nM and 22 nM in NCI-H1155 and ABC-1 cells with high N-Myc expression, respectively. GSPT1 degrader-2 can be used in the research of N-Myc-driven cancers, such as lung cancer.

ABT-002 is a molecular glue degrader targeting GSPT1 and NEK7. ABT-002 is the active metabolite of ABS-752 (HY-W599279). ABT-002 is promising for research of hepatocellular carcinoma (HCC).

PROTAC BCL6/GSPT1 Degrader-1 is a dual-target PROTAC degrader that targets BCL6 and GSPT1. PROTAC BCL6/GSPT1 Degrader-1 inhibits cell proliferation, promotes DNA damage, and induces cell cycle arrest and apoptosis in diffuse large B-cell lymphoma. PROTAC BCL6/GSPT1 Degrader-1 can be used for research on tumors such as lymphoma.

PROTAC FLT-3 degrader 5 is an orally active FLT3 PROTAC degrader with a DC₅₀ of 1.2 nM. PROTAC FLT-3 degrader 5 also acts as a molecular glue to degrade GSPT1 and IKZF1/3, with DC₅₀ values of 8.54 nM, 0.02 nM and 0.79 nM, respectively. PROTAC FLT-3 degrader 5 mediates the degradation of FLT3, GSPT1 and IKZF1/3 through interaction with the cereblon E3 ubiquitin ligase complex. PROTAC FLT-3 degrader 5 can be used in the research of acute myeloid leukemia.

GSPT1 degrader-17 is a selective GSPT1 molecular glue degrader with a DC₅₀ of 35 nM. GSPT1 degrader-17 induces GSPT1 degradation via the ubiquitin-proteasome system, which leads to G0/G1 phase cell cycle arrest and triggers apoptosis, thereby inhibiting the proliferation of leukemia cells. GSPT1 degrader-17 can be used in leukemia research.

DHC-286 is a molecular glue degrader targeting GSPT1. DHC-286 recruits GSPT1 to the CRL4CRBN ubiquitin ligase complex, promoting GSPT1 ubiquitination and proteasomal degradation, inducing cytotoxicity. DHC-286 is promising for research of cancers such as acute myeloid leukemia.